What are the current guidelines for managing sepsis?

Current Sepsis Management Guidelines

Immediate Recognition and Emergency Response

Sepsis and septic shock are medical emergencies requiring immediate treatment and resuscitation. 1, 2

Time-Critical Actions (Within First Hour)

• Administer IV antimicrobials within 60 minutes of recognizing sepsis or septic shock, as this is the single most important intervention for reducing mortality 1, 3
• Obtain at least two sets of blood cultures before antibiotics, but never delay antimicrobials beyond 45 minutes if cultures cannot be obtained 1
• Measure serum lactate immediately as a marker of tissue hypoperfusion; if elevated, remeasure within 2-4 hours 1, 4
• Begin aggressive fluid resuscitation with 30 mL/kg IV crystalloid within the first 3 hours for sepsis-induced hypoperfusion 1, 2, 4

Antimicrobial Strategy

Use broad-spectrum empiric therapy covering all likely pathogens with adequate tissue penetration to the presumed infection source 1, 2, 4

Combination Therapy Approach

• For septic shock, consider combination therapy with ≥2 antibiotics from different classes, particularly for Pseudomonas aeruginosa infections 1, 4
• Limit combination therapy to 3-5 days maximum, then de-escalate to single-agent therapy once susceptibility profiles are known 1, 4
• Review antimicrobial regimen daily for possible de-escalation 4
• Typical treatment duration is 7-10 days; longer courses may be necessary for slow clinical response or undrainable infection sites 4

Dosing Optimization

• Optimize dosing strategies based on pharmacokinetic/pharmacodynamic principles and specific drug properties 4

Hemodynamic Resuscitation

Initial Fluid Resuscitation

Use crystalloids (either balanced crystalloids or normal saline) as the fluid of choice for initial resuscitation 1, 2, 4

• Following initial 30 mL/kg bolus, guide additional fluids by frequent reassessment of hemodynamic status 1, 2
• Use dynamic rather than static variables to predict fluid responsiveness when available 5, 4
• Stop fluid resuscitation if no improvement in tissue perfusion occurs or if signs of fluid overload develop 5

Resuscitation Targets

Target mean arterial pressure (MAP) ≥65 mmHg in patients requiring vasopressors 1, 4, 3

Additional targets include:

• Normalize lactate as rapidly as possible 1, 4
• Urine output ≥0.5 mL/kg/hour 1
• Mental status improvement, capillary refill time, and resolution of mottled skin 4, 3

Vasopressor Therapy

Use norepinephrine as the first-choice vasopressor 1, 2, 3

Escalation Algorithm

1. Start norepinephrine when fluid resuscitation fails to restore adequate MAP 1
2. Add vasopressin as second-line agent if hypotension persists 1, 3
3. Add epinephrine if hypotension continues despite norepinephrine and vasopressin 1, 3

Administration Route

• Peripheral vasopressor administration through a 20-gauge or larger IV line is safe and effective 3

Source Control

Identify the anatomic source of infection and implement source control intervention as soon as medically and logistically practical, ideally within 12 hours of diagnosis 1, 2

• Perform imaging studies promptly to confirm potential infection sources 1, 2
• Use the least invasive effective approach for source control 2
• Remove intravascular access devices that are potential sources of sepsis promptly after establishing other vascular access 4

Corticosteroid Therapy

Consider IV hydrocortisone (with or without fludrocortisone) only for patients with septic shock unresponsive to fluid resuscitation and vasopressor therapy 1, 2, 3

• Avoid corticosteroids for sepsis without shock 2

Blood Product Management

Transfuse red blood cells only when hemoglobin decreases to <7.0 g/dL in the absence of extenuating circumstances and once tissue hypoperfusion has resolved 1, 2, 4

• Target hemoglobin 7-9 g/dL 1, 4
• Avoid erythropoietin for treating sepsis-associated anemia 2

Mechanical Ventilation for Sepsis-Induced ARDS

Use low tidal volume ventilation at 6 mL/kg predicted body weight 1, 4

• Limit plateau pressures to ≤30 cm H₂O 1, 4
• Apply higher PEEP in patients with moderate to severe ARDS 1
• Maintain head of bed elevated to 30-45 degrees to limit aspiration risk 4
• Use a conservative rather than liberal fluid strategy for established ARDS without tissue hypoperfusion 4

Metabolic Management

Target blood glucose ≤180 mg/dL using a protocolized approach 1

Nutrition

Initiate early enteral nutrition rather than complete fasting or IV glucose alone 1, 2

• Consider either early trophic/hypocaloric or early full enteral feeding 1, 2
• Advance feeds according to patient tolerance 5
• Consider prokinetic agents in patients with feeding intolerance 5

Specific Nutritional Recommendations

• Do not use omega-3 fatty acids as an immune supplement 5
• Do not use IV selenium 5
• Do not use glutamine 5
• Avoid arginine 5

Performance Improvement and Screening

Implement hospital-wide sepsis screening programs for acutely ill, high-risk patients 1, 2

• Use NEWS2 score to evaluate risk of severe illness or death from sepsis, interpreting scores in context of underlying physiology and comorbidities 4
• Establish multidisciplinary teams including physicians, nurses, pharmacy, and respiratory therapy 1

Goals of Care

Discuss goals of care and prognosis with patients and families, ideally within 72 hours of ICU admission 5, 1, 2

• Incorporate palliative care principles into treatment planning when appropriate 5, 1, 2

Critical Pitfalls to Avoid

• Never delay antimicrobials beyond 60 minutes while waiting for cultures or diagnostic studies 1
• Avoid inadequate initial fluid resuscitation (less than 30 mL/kg in first 3 hours) 1, 2
• Do not continue aggressive fluid administration without reassessing hemodynamic status and fluid responsiveness 5, 1
• Avoid using vasopressors without adequate initial fluid resuscitation 3
• Do not use hydroxyethyl starches for intravascular volume replacement 2
• Avoid sustained systemic antimicrobial prophylaxis in patients with severe inflammatory states of noninfectious origin (e.g., severe pancreatitis, burn injury) 4
• Do not fail to de-escalate antibiotics when appropriate based on culture results and clinical improvement 1, 4
• Avoid delayed source control for infections requiring intervention 2

Key Changes from Historical Practice

The management approach has evolved significantly over the past two decades 6:

• Movement away from routine central venous pressure and mixed venous oxygen saturation monitoring as mandatory targets 6
• Shift toward less aggressive fluid resuscitation strategies, avoiding excessive fluid administration 6
• Recognition that peripheral vasopressor administration is safe, reducing need for central access 3
• De-emphasis of routine inotrope use 6
• More restrictive red blood cell transfusion thresholds 6